This website is intended for healthcare professionals only.
Take a look at a selection of our recent media coverage:
14th April 2023
Chinese researchers have identified that lower levels of human beta-defensin-2 are significantly associated with an increased risk of a disease exacerbation in patients with chronic obstructive pulmonary disease (COPD).
Human beta-defensin 2 (hBD-2) has antimicrobial activity and is elevated in distal airways of COPD patients and may be involved in pathogenesis of the disease. Moreover, hBD2 has been shown to be reduced in the central airways of current smokers with COPD. Since human beta-defensin-2 levels are reduced in smokers with COPD, in the current study, researchers speculated on the association between hBD2 levels and disease exacerbations in COPD. In trying to establish the nature of the relationship between hBD2 and disease exacerbations, the researchers recruited patients with COPD and compared sputum levels with healthy controls. Levels of hBD2 were measured at baseline in the two groups and then after 12 and 24 months and compared. In a further analysis, researchers also compared human beta-defensin-2 levels among COPD patients who either had, or did not have, at least one symptom aggravation or disease exacerbation, over the next 2 years.
Human beta-defensin-2 levels and COPD exacerbations
A total of 203 COPD patients with a mean baseline age of 64.7 years (82% male) were compared to 51 controls who were younger (mean age = 59.5 years).
At baseline, there were no significant differences in the sputum and serum hBD-2 levels between COPD and control patients, although levels were actually slightly lower among COPD patients (2152.5 vs 1716.9 pg/mL, p = 0.057). However, when turning to COPD patients who had at least one symptom aggravation over the next 2 years, hBD2 levels were significantly lower in those who experienced an exacerbation (p = 0.001). Interestingly, sputum hBD-2 levels were not significantly different between COPD patients without an exacerbation and health controls (p = 0.626).
Using regression analysis, the researchers showed that low hBD-2 level (< 1000 pg/mL) was significantly associated with exacerbations and patients with such levels more likely to experience exacerbations over the next 12 months (p = 0.001).
They concluded that the risk of exacerbations in patients with COPD are more likely to occur when they had lower sputum hBD-2 levels, adding that these findings had important implications for future therapies for COPD.
Citation
Feng S et al. Low human beta-defensin-2 levels in the sputum of COPD patients are associated with the risk of exacerbations. BMC Pulm Med 2023
Danish researchers have found that use of drugs affecting the renin-angiotensin-system (RAS) is associated with a lower risk of both acute exacerbations and death in patients with chronic obstructive pulmonary disease (COPD).
COPD remains a major public health problem with one analysis finding that globally in 2019, there were 212.3 million cases and which accounted for 3.3 million deaths. In addition, COPD is characterised not only by local pulmonary, but also by systemic inflammation which promotes the development of extra-pulmonary and cardiovascular co-morbidities. Although traditionally used in the management of hypertension, there is emerging evidence that RAS inhibitors such as angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs) also have potential benefits in COPD patients. In fact, evidence from a retrospective analysis suggest that RAS inhibitors have dual cardiopulmonary protective properties, reducing the risk of myocardial infarction as well as COPD-related hospitalisation.
In the current study, the Danish researchers hypothesised that the use of RAS inhibitors could reduce the incidence of acute exacerbations of COPD as well as mortality in those with severe disease. Adopting a propensity-score matching approach, the team matched COPD patients prescribed a RAS drug with a similar cohort of COPD patients given bendroflumethiazide as an active comparator. The primary outcome was severe acute exacerbations of COPD within 12 months after study entry or death in the same period.
RAS inhibitor use and COPD outcomes
A total of 3029 patients with a median age of 72 years (69.1% female) and prescribed either an ACEi or ARB and propensity matched to a similar number prescribed bendroflumethiazide.
The use of either an ACEi or ARB was associated with a 14% lower risk of exacerbations or death compared to those using bendroflumethiazide (hazard ratio, HR = 0.86, 95% CI 0.78 – 0.95). This reduced risk was also evident in a sensitivity analysis of the propensity-score-matched population (HR = 0.89, 95% CI 0.83 – 0.94) and in an adjusted Cox proportional hazards model (HR = 0.93, 95% CI 0.89- 0.98).
The authors concluded that use of RAS inhibitor treatment lowered the risk of both acute exacerbations and death in those with COPD. However, they added the caveat that while there is a biologically plausible explanation for this finding, randomised controlled trials were needed to confirm this effect, given the observational nature of their study.
Citation
Vilstrup F et al. Renin-angiotensin-system inhibitors and the risk of exacerbations in chronic obstructive pulmonary disease: a nationwide registry study. BMJ Open Respir Res 2023
13th April 2023
Dupilumab treatment for 12 months leads to the lowest number of exacerbations and better improvements in FEV1 compared to two commonly used monoclonal antibodies (mAbs), omalizumab or mepolizumab, in adults with moderate to severe asthma, according to comparative analysis by US researchers.
The prevalence of severe asthma varies between 3.6 and 6.1% of all patients with the disease. Individuals with moderate to severe asthma have the opportunity of being treated with several monoclonal antibodies, which target key inflammatory cytokines involved in disease pathogenesis. All of these currently approved biologic therapies have been shown to improve asthma-related outcomes in individuals with asthma uncontrolled with conventional therapy. However, for patients with more than one phenotype such as allergic and eosinophilic asthma, trying to identify the most suitable agent is less clear. In the absence of direct head-to-head comparative trials, researchers can often utilise observational data to emulate a hypothetical pragmatic randomised trial, which is referred to as the target trial.
In the current analysis, the research team emulated a hypothetical randomised trial, making use electronic health records from a large US-based academic health care system. They included adult participants with baseline IgE levels between 30 and 700 IU/mL and peripheral eosinophil counts of at least 150 cells/μL with the objective of comparing the effectiveness of dupilumab treatment with omalizumab or mepolizumab in patients with moderate to severe asthma. The main outcomes of interest were the incidence of asthma-related exacerbations and the change in baseline FEV1 value over 12 months of follow-up.
Dupilumab treatment and asthma outcomes over 12 months
In all, 68 individuals received dupilumab treatment 68 received omalizumab and 65 received mepolizumab.
Over the 12 month period of follow-up, asthma-related exacerbations occurred in 25.0% of those receiving dupilumab treatment compared to 43.1% for mepolizumab (adjusted hazard ratio, aHR = 0.35, 95% CI 0.18 – 0.71). Compared to omalizumab group, asthma exacerbations occurred in 39.7% of patients, giving a corresponding adjusted hazard ratio of 0.42 (95% CI 0.20 – 0.87).
The change in FEV1 for the different agents were 0.11 L (95% CI -0.003 to 0.222 L) for dupilumab versus mepolizumab and 0.082 L (95% CI -0.040 to 0.204 L) for dupilumab versus omalizumab.
In patients with eosinophil counts of at least 300 cells/μL, the HR for dupilumab compared to mepolizumab was 0.26 (95% CI 0.10 – 0.67) and 0.24 (95% CI 0.09 – 0.63) for dupilumab vs omalizumab.
Based on these findings, the authors concluded that among patients with asthma and eosinophil counts of at least 150 cells/μL and IgE levels of 30 to 700 kU/L, dupilumab was associated with greater improvements in exacerbation and FEV1 value than either omalizumab or mepolizumab.
Citation
Akenroye AT et al. Comparative effectiveness of omalizumab, mepolizumab, and dupilumab in asthma: A target trial emulation. J Allergy Clin Immunol 2023
Bimekizumab appears to be an effective treatment for patients with hidradenitis suppurativa, according to the findings of a phase 3 trial.
Hidradenitis suppurativa (HS) is a chronic inflammatory disorder affecting intertriginous areas of skin. and affects around 1% of the population. Clinically, patients experience cutaneous inflamed nodules, abscesses and pus-discharging tunnels that develop in axillary, inguinal, gluteal and perianal body sites.
There is often a diagnostic delay and which leads to more severe disease. Bimekizumab is a humanised, monoclonal antibody that selectively inhibits both IL-17A and IL-17F. A phase 2 trial found use of the drug led to clinically meaningful improvement in patients with HS.
In the recent study, data from two phase 3, randomised, placebo-controlled trials in adult patients with moderate to severe HS. Both trials had a 16-week initial and 32-week maintenance treatment period.
Bimekizumab was used at a dose of 320 mg every two weeks and 320 mg every four weeks. The Hidradenitis Suppurativa Clinical Response (HiSCR50) served as the primary outcome measure. This is defined as a 50% decrease in the total abscess and inflammatory nodule count, with no increase in abscess or draining tunnel count.
There were 1,014 patients in the two trials. In both trials at week 16, more patients using bimekizumab achieved the primary outcome compared to placebo. For example, 45.3% vs28.7%, p = 0.030 (BE HEARD 1) and 53.8% vs 32.2%, p = 0.004 ( BE HEARD II). These improvements were seen for both drug regimens. In addition, over 75% percent of patients using bimekizumab achieved HiSCR50 and over 55% a HiSCR75 at week 48.
The company will submit data for global regulatory approval of the drug in patients with moderate to severe HS later in 2023.
According to Chinese researchers and based on an analysis of individuals in the UK Biobank, having a healthy sleep pattern appears to mitigate the effect of genetic susceptibility to asthma.
Asthma is a chronic respiratory inflammatory disease and which globally, has been estimated to affect between 9.8 and 17.9% of the population depending on whether the definition includes wheezing or ever wheeze. Although there are a number of potential causes of asthma including a family history and exposure to various allergens, the presence of a persistent short sleep duration is one factor identified as being associated with an increased risk of developing asthma. While genome-wide association studies have revealed some asthma loci, the variability of genetic influence suggests that several other, non-genetic exposures may also influence the development of asthma.
In the current study, researchers examined the association between sleep traits, genetic susceptibility and the risk of asthma in a UK Biobank cohort. The team undertook an analysis of those aged 38-73 years and for whom polygenic risk scores and comprehensive sleep scores, were constructed. The researchers used a multivariable Cox proportional hazard regression model to investigate the independent and combined effects of sleep pattern and genetic susceptibility on asthma incidence. Participants were assigned as being at a low, intermediate and high risk of asthma based on genetic susceptibility and sleep categorised as ‘healthy’, ‘intermediate’ and ‘poor’.
Healthy sleep pattern and development of asthma
From a total of 455,405 individuals with a mean age of 56.5 years (54% female), 17,836 were diagnosed with asthma during over 10 years of follow-up.
Compared with those deemed to be a low genetic risk, the hazard ratio (HR) for those with the highest genetic risk was 1.47 (95% CI 1.41 – 1.52) for the development of asthma. Similarly, among those with poor sleep, there was also an elevated risk for asthma (HR = 1.55, 95% CI 1.45 – 1.65). In addition, among those with a high genetic risk and categorised as having poor sleep, there was a more than two-fold increased risk of developing asthma (HR = 2.22, 95% CI 1.97 – 2.49, p < 0.001).
However, in further analysis, researchers found that a healthy sleep pattern was associated with a lower risk of asthma in all three genetic susceptibility groups. For example, a healthy sleep pattern reduced the risk of developing asthma by 44% (HR = 0.56) among those at a low genetic risk and by 37% in those at high genetic risk (HR = 0.63). In fact, the researchers calculated that at the population level, a low genetic risk and a healthy sleep pattern could reduce the risk of asthma cases by up to 19%.
The authors concluded that a healthy sleep pattern reflected a lower risk of asthma in adult populations and could be beneficial to asthma prevention regardless of genetic conditions.
Citation
Xiang B et al. Highlighting the importance of healthy sleep patterns in the risk of adult asthma under the combined effects of genetic susceptibility: a large-scale prospective cohort study of 455 405 participants. BMJ Open Respir Res 2023
11th April 2023
UK and Japanese researchers have shown that among infants with atopic eczema, enhanced treatment, i.e., to both clinically affected and unaffected skin, is more effective at preventing hen’s egg allergy than conventional or reactive treatment, applied only to clinically affected areas.
There appears to be an increase in the prevalence of food allergy in some areas of the world, thus highlighting the need for better strategies for prevention, diagnosis and therapy. For example, one study of Japanese children found a caregiver-reported immediate food allergy prevalence of 7.6% in children aged 1, with hen egg allergy being the most common at 5.4%. The presence of atopic eczema is associated with the development of food allergies, with a suggestion that infants with early eczema onset (within the first 1 – 4 months after birth) have an increased risk of developing food allergy at 3 years of age. Given the relationship between atopic eczema and food allergies, researchers wondered if early treatment of the disease could reduce the subsequent development of allergies. One retrospective analysis showed that early aggressive use of topical corticosteroids to shorten the duration of atopic eczema in infants, was associated with decreased development of food allergy by 24 months of age.
Based on the findings of this retrospective analysis, in the current study, researchers conducted a randomised controlled trial. Infants aged 7-13 weeks with atopic eczema were treated with topical steroids and randomised 1:1 to enhanced early skin treatment or conventional reactive treatment, i.e., applying topical corticosteroids only to areas of clinically affected skin. The team set the primary outcome as the proportion of immediate hen’s egg allergy confirmed by oral food challenge at 28 weeks of age.
Enhanced early treatment and the development of hen’s egg allergy
A total of 640 children were included, 318 of whom were assigned to enhanced early treatment. Two-thirds (66%) of children in the enhanced group were aged 7 to 10 weeks at enrolment.
Enhanced treatment significantly reduced hen’s egg allergy compared with the conventional treatment (31.4% vs. 41.9%, p = 0.0028). However, a higher proportion of infants in the enhanced group experienced serious adverse events (5.3% vs 1.9%). In addition, the intervention reduced mean body weight and height when assessed at week 28.
The authors concluded that while enhanced control of atopic eczema appeared to reduce hen’s egg allergy, the treatment protocol of this trial should be modified in order to avoid the adverse effects of topical corticosteroids.
Citation
Yamamoto-Hanada K et al. Enhanced early skin treatment for atopic dermatitis in infants reduces food allergy. J Allergy Clin Immunol 2023
6th April 2023
A systemic review has found that an AI model provides similar diagnostic ability for hip fractures to that of expert radiologists.
In a systemic review and meta-analysis, Canadian researchers found that the performance of an artificial intelligence (AI) model for the diagnosis of hip fractures was comparable with that of expert radiologists and surgeons.
Artificial intelligence (AI) models being increasing used for a range of healthcare applications, although the evidence for a beneficial effect on clinician diagnostic performance is spare.
In contrast, models based on deep learning algorithms offer some promise for diagnostic purposes with findings to date suggesting that the diagnostic performance of such systems are equivalent to that of health-care professionals.
With hip fractures associated with a huge morbidity and mortality, how useful is an AI model (AIM) for the automatic identification and classification of hip fractures and how does this compare with clinicians were the questions addressed by researchers in the current study.
The team performed a systematic review of the literature and included studies that involved the development of machine learning models for the diagnosis of hip fractures from hip or pelvic radiographs or to predict any postoperative patient outcome following hip fracture surgery.
The team examined the diagnostic accuracy of an AIM in comparison to expert clinicians and used the areas under the curve (AUC) for postoperative outcome prediction such as mortality between traditional statistical models and that developed by the machine learning models.
A total of 39 studies were included, of which 46.2% used an AIM to diagnose hip fractures on plain radiographs and 53.8% used an AIM to predict patient outcomes following hip fracture surgery.
When compared with clinicians, the odds ratio for diagnostic error of the AI models was 0.79 (95% CI, 0.48 – 1.31 p = 0.36) for hip fracture radiographs. In other words, although the analysis favoured an AIM, statistically, models were no better than clinicians.
In addition, the mean sensitivity for the model was 89.3% and the specificity 87.5% and the F1 score (which that assesses the model’s accuracy) was 0.90 (range 0 to 1.0).
For post-operative predictions, e.g., such as mortality, the mean AUC was 0.84 with AI models and 0.79 for alternative controls and therefore not significantly different (p = 0.09).
The authors concluded that while promising for the diagnosis of hip fractures, the performance of AI models was comparable with that of expert radiologists and surgeons, adding that AI outcome prediction appears to provide no substantial benefit over traditional multivariable predictive statistics.
Citation
Lex JR et al. Artificial Intelligence for Hip Fracture Detection and Outcome Prediction: A Systematic Review and Meta-analysis. JAMA Netw Open 2023.
Norwegian researchers have found that oral vitamin D supplementation given throughout the winter months to patients with psoriasis, despite increasing serum levels of the vitamin, does not lead to an improvement in disease severity.
One aspect of treatment for psoriasis involves the use of topical vitamin D although whether oral vitamin D is also an effective form of therapy remains to be clarified. One randomised trial concluded that oral vitamin D2 increased both serum vitamin D levels and disease severity.
Nevertheless, in a systematic review of 7 studies (only three of which were quantitative), the authors concluded that a favourable effect of oral vitamin D supplementation in patients with psoriasis could not be verified but called for more randomised trials to address this issue. However, the available studies did not consider a seasonal effect since vitamin D is produced in the skin by the action of UVB radiation.
In the present trial, researchers focused on trying to establish whether oral vitamin D provided during the winter months, given to psoriasis patients with low serum levels of the vitamin, would have a beneficial effect on disease severity.
The study recruited adult patients with active plaque psoriasis and 25-hydroxyvitamin D (25[OH]D) levels of less than 24 ng/mL. Cholecalciferol (oral vitamin D) was given at a loading dose of 100 000 IU, followed by 20 000 IU/week or matching placebo, for a period of 4 months.
The primary outcome was the change in the Psoriasis Area Severity Index (PASI) score, which is a measure of disease severity. The researchers also looked at the change in Dermatology Life Quality Index scores.
Oral vitamin D supplementation and psoriasis disease severity
A total of 122 participants with a mean age of 53.6 years (37.7% female) were randomised to either oral supplementation (60) or placebo. The mean baseline PASI score was 3.1.
After 4 months, the mean 25(OH)D level was 29.7 ng/mL and 12.0 in the placebo group. However, while serum levels of vitamin D had increased among participants in the intervention arm, there was no significant difference in the PASI score between the groups (adjusted difference, AD = 0.11, 95% CI -0.23 to 0.45, p = 0.52). In addition, there was no significant difference in DLQI scores between the groups (AD = -0.86, 95% CI -1.9 to 0.19, p = 0.11).
The authors concluded that oral vitamin D supplementation did not affect psoriasis severity and suggested that low baseline severity scores might have accounted for lack of measurable effect.
They also added that since less than half of the intervention group achieved a serum 25(OH)D level of 30 ng/ml, this may have affected the results.
Citation
Jenssen M et al. Effect of Vitamin D Supplementation on Psoriasis Severity in Patients With Lower-Range Serum 25-Hydroxyvitamin D Levels: A Randomized Clinical Trial. JAMA Dermatol 2023
In a press release from the manufacturer Karuna Therapeutics, it was announced that its lead investigational therapy, xanomeline-trospium, demonstrated a statistically significant and clinically meaningful reduction in Positive and Negative Syndrome Scale (PANSS) total score compared to placebo, in adults with schizophrenia.
Schizophrenia is a psychotic disorder characterised by positive symptoms, such as hallucinations, delusions, formal thought disorders, and negative symptoms, such as paucity of speech, anhedonia, and lack of motivation. Xanomeline is a muscarinic agonist (M1 and M4) and has been shown to improve all symptoms types of schizophrenia. However, drug development was stopped due to the severe cholinergic adverse effects but when used in combination with the peripheral cholinergic antagonist, trospium, it is expected that the latter can reduce the adverse effects of xanomeline. Early findings to date have been positive and in a 5-week trial, randomised, double-blind, placebo-controlled trial, xanomeline-trospium produced a greater decrease in the PANSS total score than placebo 2.
The current press release relates to the EMERGENT-3 Trial, a phase 3, randomised, double-blind, parallel-group, placebo-controlled, multicentre study, with xanomeline-trospium in patients with schizophrenia. The primary objective was to assess the efficacy of xanomeline-trospium (125 mg xanomeline and trospium chloride 30 mg) given twice daily, at reducing Positive and Negative Syndrome Scale (PANSS) total scores in adult inpatients with a DSM-5 diagnosis of schizophrenia.
A total of 256 adults (between the ages of 18-65 years) with schizophrenia were included in the trial and were experiencing symptoms of psychosis at the time of enrolment. In the trial, patients were randomised 1:1 to receive either a flexible dose of xanomeline-trospium or placebo twice daily for five weeks. On days 1-2, patients received a dose of 50mg xanomeline/20mg trospium) twice daily or matching placebo. On Day 3, patients escalated to a dose of 100/20 twice daily and on Day 8, patients had the option to increase to 125/30 twice daily, based on tolerability.
Xanomeline-trospium in EMERGENT-3
The trial met its primary endpoint, with xanomeline-trospium showing a statistically significant and clinically meaningful 8.4-point reduction in Positive and Negative Syndrome Scale (PANSS) total score compared to placebo (-20.6 vs. -12.2 placebo, p < 0.0001) at Week 5. In fact, the combination demonstrated an early and sustained statistically significant reduction of symptoms from Week 2 (p < 0.05) through the end of the trial as assessed by PANSS total score.
The overall discontinuation rate in the trial was 33% (37% xanomeline-trospium vs. 29% placebo) with the overall treatment emergent adverse event (TEAE) rates slightly higher for the combination compared to placebo (70% vs 50%).
The press release also reports that the company will submit data to the FDA mid-2023 and hopefully, if approved will look to launch the drug in 2024.
In a case-controlled study, Iranian researchers have determined that drinking black or green tea, coffee and non-alcoholic beverages are associated with a lower risk of developing multiple sclerosis (MS), whereas in contrast, for instance, a higher intake of carbonated beverages, increases the risk.
Multiple sclerosis (MS) is the most common cause of neurological disability in young adults worldwide and a 2020 study estimated that, globally, some 2.8 million people are living with the condition. Although the underlying cause remains uncertain, there is evidence that certain dietary factors may have an effect. For example, the consumption of alcoholic beverages, coffee and fish have been shown to be inversely associated with progression of disability in relapsing onset MS, but not in progressive onset MS. In fact, it has been suggested that a high coffee consumption may decrease the risk of developing MS. While it is known that polyphenolic compounds such as resveratrol exhibit several other biological/biochemical protective effects on the heart, circulation, brain and age-related diseases, the Iranian researchers wondered if black or green tea (which also contains several polyphenols) may exert a protective effect in MS.
The researchers performed case-control study on 150 patients with MS and 300 healthy individuals who served as a control group. Data on demographic and beverage consumption was collected by a questionnaire and analysed by univariate and multiple logistic regression models.
Black or green tea and multiple sclerosis
The mean age of the MS patients was 38.6 years (80.1% female) which was similar for the control group, (37.2 years) although there were less women (58.5%).
The results showed that drinking black tea was significantly associated with a reduced risk of developing MS (Odds ratio, OR = 0.20, 95% CI 0.10 – 0.37, p < 0.001), as was drinking green tea (OR = 0.29, 95% CI 0.13 – 0.63, p = 0.002), coffee (OR = 0.07) and non-alcoholic beer (OR = 0.48)
In contrast, consumption of natural juice or (OR = 2.49), milk (OR = 5.46) and carbonated beverages (OR = 16.17) were all associated with an increased odds of developing MS.
The researchers acknowledged that a limitation of the study design was the possibility of memory bias and consequently suggested that their findings could be used to design interventional research and to change people’s lifestyles to prevent MS.
Citation
Dastoorpoor M et al. A case-control study of drinking beverages and the risk of multiple sclerosis in Iran. J Health Popul Nutr 2023
IMPORTANT LINKS
MORE FROM COGORA
© Cogora 2025
Cogora Limited. 1 Giltspur Street, London EC1A 9DD
Registered in the United Kingdom. Reg. No. 2147432
